Acute Lymphoblastic Leukemia in a Patient With Constitutional Chromosome 1pter-p36.31 Duplication and 1q43-qter Deletion

Abstract

Chromosome 1 is the largest of all human chromosomes, containing 3141 genes. It is linked to 890 known genetic diseases including congenital hypothyroidism, hemochromatosis, and prostate cancer. Recognized deletion and duplication syndromes have been described. Deletions in the short arm (p) of the chromosome have been identified in tumors of the brain and kidneys. Duplications in the long (q) arm of the chromosome are reported in myelodysplastic syndromes. Solitary 1p36 deletion or 1q42 duplication are rarely reported entities and their associations with malignancy have not been characterized. We report a case of a child with constitutional 1pter-p36.31 duplication and 1q43-qter deletion who developed acute lymphoblastic leukemia (ALL). The patient's oncologic presentation and subsequent clinical course raise the question of the association of the underlying genetic abnormality and its malignant potential, specifically in relation to ALL. Acquired chromosome 1 deletions and duplications have been well described in other malignant diseases. Constitutional chromosome 1p duplication and 1q deletions have not been described with ALL.

Neonatal Pancytopenia Associated With De Novo 1q43-44 Deletion and 10p15 Duplication

“…The candidate FLI-1 gene is believed to be responsible for the dysmegakaryopoiesis suggesting a pathogenic role for the FLI-1 gene in the pathophysiology of the platelet abnormalities. 1 Our patient's predisposition to cancer is supported by the detection of increased amounts of immature cells in her bone marrow aspirate. 24 Moreover, patients with interstitial microdeletion syndromes involving 1q21.1 are associated with the thrombocytopenia-absent radius syndrome.…”

“…1 Distal trisomy 10p15, which has rarely been reported in the literature, has been associated with a mild phenotype 19 and no pancytopenia. In contrast, none of these published cases showed a 1q partnership with 10p.…”

“…1 The patient we describe presented with classic features of both 1q43-44 microdeletion syndrome and trisomy 10p as well as chronic pancytopenia of unknown etiology from birth. Many patients with individual microdeletion 1q43-44 syndrome or duplication of short arm of chromosome 10 have been previously described.…”

“…1 Pancytopenia in a neonate is a rare condition. Notably, neither of these genetic aberrations is currently known to be associated with hematologic derangements except in the most recent publication of 1q43 deletion/1p36 duplication associated with acute lymphoblastic leukemia.…”

Familial Duplication/Deletion of 1q42.13q43 as Meiotic Consequence of an Intrachromosomal Insertion in Chromosome 1

“…Most of the reported cases are the results of translocations involving the telomeric regions of chromosomes [Steffensen et al, 1977;Johnson et al, 1985;Watson et al, 1986;Kausch et al, 1988;Johnson, 1991;Ioan et al, 1992;Arai et al, 1994;Concolino et al, 1998;Fan et al, 1999;Bartsch et al, 2001;De Brasi et al, 2001;Gentile et al, 2003;Coccé et al, 2007;Hill et al, 2007;Tuschl et al, 2007;Chen et al, 2010Chen et al, , 2012Tartaglia et al, 2011;Khan et al, 2012;Morris et al, 2016].…”